Lyme disease is a spirochetosis transmitted by the bite of Ixodes dammini ticks. It is characterized by an annular skin lesion, usually starting at the site of tick attachment, known as erythema chronicum migrans (ECM) and, in decreasing order of frequency, by arthritis usually of the large joints, neurological and cardiac complications. The pathogenic relationships between infection with the Lyme diseases spirochete (LDS) and the development of skin lesions and arthritis are not yet understood. It is the purpose of these studies to explore those relationships by investigating model skin and joint lesions produced in the rabbit by exposure to the LDS. In so doing a more general understanding of arthritis produced by bacterial infection should result. ECM will be produced by attachment of infected ticks and by intradermal injection of motile LDS. In addition, an attempt will be made to induce a skin lesion with a proteinaceous extract of tick salivary glands in order to study the role of tick factors in the development of ECM. LDS will be physically and chemically fractionated to yield the outer envelope (OE), peptidoglycan (PG) and lipopolysaccharide (LPS) constituents. These moieties will be tested for their ability to initiate a skin lesion. The OE includes most of the antigenic determinants of whole LDS while LPS has potent inflammatory and immunoregulatory effects. The PG derived from other bacterial species have systemic toxicity when administered in small doses. Skin lesions will be biopsied and characterized histologically with respect to the nature of the inflammatory cell infiltrate. Other lesions will be used for the artificial induction of blisters. Fluid from the blisters will be analyzed for the presence of inflammatory mediators including leukotriene B4, histamine and interleukin 1. LDS and their fractions will also be injected intraarticularly in the rabbit knee for the induction of arthritis. At various times after exposure the knees will be examined for signs of inflammation. Synovial fluid will be harvested and characterized with respect to the cellular content as well as for the presence of inflammatory mediators including leukotriene B4, interleukin 1, histamine, prostaglandin E2 and collagenase. Animals will be sacrificed and the histopathology of the arthritic lesions in the synovium, cartilage and adjacent bone characterized.